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PURPOSE There is a lack of published literature on systemic therapeutic options in cisplatin-ineligible patients with locally advanced head and neck squamous cell carcinoma (LAHNSCC) undergoing chemoradiation. Docetaxel was assessed as a radiosensitizer in this situation. METHODS This was a randomized phase II/III study. Adult patients (age ≥ 18 years) with LAHNSCC planned for chemoradiation and an Eastern Cooperative Oncology Group performance status of 0-2 and who were cisplatin-ineligible were randomly assigned in 1:1 to either radiation alone or radiation with concurrent docetaxel 15 mg/m2 once weekly for a maximum of seven cycles. The primary end point was 2-year disease-free survival (DFS). RESULTS The study recruited 356 patients between July 2017 and May 2021. The 2-year DFS was 30.3% (95% CI, 23.6 to 37.4) versus 42% (95% CI, 34.6 to 49.2) in the RT and Docetaxel-RT arms, respectively (hazard ratio, 0.673; 95% CI, 0.521 to 0.868; P value = .002). The corresponding median overall survival (OS) was 15.3 months (95% CI, 13.1 to 22.0) and 25.5 months (95% CI, 17.6 to 32.5), respectively (log-rank P value = .035). The 2-year OS was 41.7% (95% CI, 34.1 to 49.1) versus 50.8% (95% CI, 43.1 to 58.1) in the RT and Docetaxel-RT arms, respectively (hazard ratio, 0.747; 95% CI, 0.569 to 0.980; P value = .035). There was a higher incidence of grade 3 or above mucositis (22.2% v 49.7%; P < .001), odynophagia (33.5% v 52.5%; P < .001), and dysphagia (33% v 49.7%; P = .002) with the addition of docetaxel. CONCLUSION The addition of docetaxel to radiation improved DFS and OS in cisplatin-ineligible patients with LAHNSCC. [Media: see text]

Parotid fistula after surgery for oral cancer is a less commonly recognized and less reported complication. In this study, we aimed to report its incidence and identify factors predisposing patients to it and the management of the patients in our cohort.This was a retrospective study of treatment-naive patients with oral cancer who underwent surgery from January 2019 to December 2020 in a single unit of our institute. Patients who were operated for recurrence and second primary were excluded.A total of 434 patients were included in the study. Most were men (n = 352; 81.1%) and presented with an advanced clinical stage (n = 318; 73.2%). The incidence of parotid fistula in our study was 6.9% (n = 30 of 434). Buccal mucosa/gingival buccal sulcus subsite (P = .05; odds ratio [OR] = 3.423; 95% CI, 0.969-12.087) and advanced clinical T stage (P = .003; OR = 6.15; 95% CI, 1.835-20.608) were the 2 most important factors predisposing patients to the development of parotid fistula after surgery for oral cancer.Parotid fistula is a less common complication after surgery for oral cancer. A conservative treatment approach is usually successful in treating this complication.

PURPOSE The objective of this study was to explore the potential role and safety of neoadjuvant chemotherapy (NACT) in tumor shrinkage and resultant mandibular preservation in oral cancers compared with conventional surgical treatment. METHODS This study was a single-center, randomized, phase II trial of treatment-naive histologically confirmed squamous cell carcinoma of the oral cavity with cT2-T4 and N0/N+, M0 (American Joint Committee on Cancer, seventh edition) stage, necessitating resection of the mandible for paramandibular disease in the absence of clinicoradiologic evidence of bone erosion. The patients were randomly assigned (1:1) to either upfront surgery (segmental resection) followed by adjuvant treatment (standard arm [SA]) or two cycles of NACT (docetaxel, cisplatin, and fluorouracil) at 3-week intervals (intervention arm [IA]), followed by surgery dictated by postchemotherapy disease extent. All patients in the IA received adjuvant chemoradiotherapy, and patients in the SA were treated as per final histopathology report. The primary end point was mandible preservation rate. The secondary end points were disease-free survival and treatment-related toxicity. RESULTS Sixty-eight patients were enrolled over 3 years and randomly assigned to either SA (34 patients) or IA (34 patients). The median follow-up was 3.6 years (interquartile range, 0.95-7.05 years). Mandibular preservation was achieved in 16 of 34 patients (47% [95% CI, 31.49 to 63.24]) in the IA. The disease-free survival ( P = .715, hazard ratio 0.911 [95% CI, 0.516 to 1.607]) and overall survival ( P = .747, hazard ratio 0.899 [95% CI, 0.510 to 1.587]) were similar in both the arms. Complications were similar in both arms, but chemotherapy-induced toxicity was observed in the majority of patients (grade III: 14, 41.2%; grade IV: 11, 32.4%) in the IA. CONCLUSION NACT plays a potential role in mandibular preservation in oral cancers with acceptable toxicities and no compromise in survival. However, this needs to be validated in a larger phase III randomized trial.

Recurrent laryngeal nerve (RLN) palsy is one of the feared complications following thyroid surgery. Intraoperative neuromonitoring (IONM) has been used as an adjunct to reduce this complication. In the present study, we attempted to evaluate the IONM parameters such as latency, current requirement, and baseline amplitude that could predict temporary RLN palsy along with factors that could influence these parameters during thyroid surgery. This was a retrospective study of patients who underwent hemi, total, or completion thyroidectomy for cancer at our institute between June 1, 2017 to May 31, 2019 in whom IONM was used during surgery. The study consisted of 84 consecutive patients with 138 nerves at risk. The RLN palsy rate in our study was 5% (n = 7). Patients with low baseline amplitude and/or requiring higher current to maintain normal baseline amplitude were often associated with temporary RLN palsy. In the multivariate analysis, age > 40 years (p = 0.001, OR = 4.14) influenced the baseline EMG amplitude the most. The intraoperative current management was influenced by advanced pT stage (p = 0.001, OR = 2.87), and structural nerve injury (p = 0.001, OR = 3.15). Patients with low baseline amplitude and/or requiring higher current to maintain normal baseline amplitude were often associated with temporary RLN palsy. Factors such as age, pT stage, and structural nerve injury influenced the IONM stimulation and recording parameters.

Context Tumors of parapharyngeal space (PPS) are rare and histologically diverse. The management of these tumors requires diligent assessment and planning with due consideration of various anatomical and pathological aspects of the lesion. Aims This retrospective study aims to present our experiences in the clinical and pathological aspects of PPS tumors with a critical evaluation of management. Settings and Design Retrospective analytical study. Methods and Material The electronic medical records of 60 cases of PPS tumors, managed surgically from 2007 to 2017, were reviewed and analyzed using SPSS 22 software. The mean follow-up duration was 44 months. Results The mean age was 45 years with a male-to-female ratio of 1.7 (38:22). The majority of the tumors were benign (71.7%) and the most common presentation being upper neck mass or oropharyngeal mass. Histologically, neurogenic tumors were most common (43.3%) PPS tumors, followed by tumors of salivary gland origin. Magnetic resonance imaging was used as a diagnostic modality in 70% of cases, and computed tomography scan and positron emission tomography/CT were used in 26.7 and 3.3% of cases, respectively. In our study, the diagnostic accuracy of fine-needle aspiration cytology was 71% for benign and 47% for malignant lesions. The most common approach for surgery used was transcervical (72%). Conclusion The study reveals that cranial nerve palsy is the most common complication associated with PPS tumors. Completely resected, malignant tumors originating within PPS have a good prognosis, as compared with tumors extending or metastasized to PPS.

Despite advancements in technology and increase in favorable outcomes associated with oral cancer, early detection remains the most significant factor in limiting mortality. The current study aimed to develop early diagnostic and prognostic markers for oral tumorigenesis. Protein and ultrastructural alterations at cell-extracellular matrix (ECM) adhesion junctions were examined concurrently using immunohistochemistry (IHC) and transmission electron microscopy (TEM) on progressive grade of oral carcinomas (n = 285). The expression of hemidesmosome (HD) proteins-integrin β4, BP180, and laminin-5 increased in hyperplasia as compared to normal, and significantly increased further, as the disease progressed. TEM analysis in parallel tissues revealed a significant decrease in HD number and increase in the length of basal lamina (BL) in hyperplasia. With cancer progression, the severity of ultrastructural alterations increased gradually and significantly. Overexpression of HD proteins, decrease in HD number and increase in BL length significantly correlated with nodal metastasis, local recurrence, and recurrence-free survival of patients. Concurrent use of IHC and TEM can add value to early recognition of neoplastic changes in primary carcinomas of oral cavity. In this regard, altered expression of integrin β4 and laminin-5, loss of HDs, and increased BL length could offer criteria for early diagnosis and prognosis of oral malignancy.

Laryngeal neuroendocrine neoplasms (NENs) are rare and heterogeneous, encompassing well-differentiated neuroendocrine tumors (NETs; grade 1, 2, and 3), neuroendocrine carcinomas (NECs, small cell and large cell types), and mixed neuroendocrine non-neuroendocrine neoplasms (MiNEN). We aimed to study the clinicopathologic spectrum of these neoplasms. A retrospective review of all primary laryngeal NENs diagnosed from 2005 to 2017 was undertaken. Mitotic index was divided into 10 mitoses/2 mm(2), with a Ki-67 labelling index of 20% for the NET grade 1, 2 and 3 categories, respectively. A total of 27 patients were included. The median age at presentation was 60 years; the male-to-female ratio was 8:1. Supraglottis (n = 22) was the most frequently affected subsite. There were 9 NETs grade 2 (G2), and 18 NECs cases. There were no NET grade 1 or 3 cases in our cohort. Among the NETs G2, the morphology was epithelioid (2), plasmacytoid (3), clear (2), oncocytic (1), and rhabdoid (1). Unique ‘glomeruloid structures’ (n = 5), calcification (n = 3), lymphoid aggregates (n = 5), intranuclear inclusions (n = 2), hyaline globules (n = 3), and Leisegang rings (n = 2) were identified. NECs comprised 16 small cell neuroendocrine carcinoma and 2 large cell neuroendocrine carcinoma. On immunohistochemistry, tumor cells expressed AE1/AE3 (86%), synaptophysin (100%), chromogranin (100%), INSM1 (100%), calcitonin (33.3%). In the NEC group, p53 aberrant expression (87.5%), Retinoblastoma (Rb) loss (88.2%), and diffuse p16 immunoreactivity (66.7%) were additionally observed. Lymph-node metastasis was detected in 62.5% and 85.7%, while distant metastasis in 55.6% and 76.9%, respectively in NET G2 and NEC. Laryngeal NENs are aggressive neoplasms with a high rate of nodal and distant metastasis. Awareness of the wide pathologic spectrum of laryngeal NENs and appropriate use of IHC is needed to render an accurate diagnosis. Ki67 assessment is strongly recommended for laryngeal NEN prognostication SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12105-021-01367-9.

Background Microvascular reconstruction after oncologic resection with curative intent in recurrent or second primary cancer cases is challenging not only because of the complexity of the defect but also due to difficulty in finding suitable donor vessels in the neck that has already been subjected to surgery and subsequent adjuvant treatment. In our present study, we evaluated the success of free flaps, reexplorations, and factors associated with reexploration and with flap failures in previously operated and/or radiated neck. Methods In this retrospective study, we analyzed patients who underwent microvascular reconstruction from January 2016 to December 2018 in patients with previous surgery and/or radiation, considered as "already treated neck" (ATN). These cases were reviewed to analyze variables that included age, sex, indication for surgery (recurrence, second primary, osteoradionecrosis, and secondary reconstruction), duration since previous surgery or radiation, free flap done, donor vessels used, the need to go to the contralateral neck or outside the neck, need for vein grafts, flap reexploration rate, flap survival rate, and hospital stay of the patients. We also tried to identify factors that predisposed for a reexploration after performing reconstruction with a free flap in ATN. Results Of 1522 free flaps done, 371 patients were included in the study. Flap success rate was 90.8% in ATN, which was comparable to naive neck (94%; P = 0.108). The reexploration rate in ATN (16.2%) was significantly higher (P = 0.0003) than in naive neck (9.8%). The previous treatment (neck dissection) received [P = 0.001; odds ratio, 13.7 (1.87-101.6)] was the most significant predisposing factor, and patients undergoing osteocutaneous flaps were more prone to undergo reexplorations (P = 0.05). Side of anastomosis, vessel used for anastomosis, comorbidities, and time since previous treatment did not affect the reexploration rate significantly. Conclusions Microvascular reconstruction can be safely performed in ATN with good success rates, and it should not be a deterrent in whom free flap is required to achieve best functional outcome. However, it may be associated with increase in reexploration rates in the postoperative period. Patients having undergone a previous neck dissection are at more risk of undergoing this reexploration in comparison with radiotherapy (RT)/chemotherapy and radiotherapy (CTRT) alone.

Ensuring the integrity of the recurrent laryngeal nerve (RLN), the external branch of superior laryngeal nerve (EBSLN) and preservation of normal voice are the prime 'functional' goals of thyroid surgery. More in-depth knowledge of neuronal mechanisms has revealed that anatomical integrity does not always translate into functional integrity. Despite meticulous dissection, neural injuries are not always predictable or visually evident. Intraoperative nerve monitoring (IONM) is designed to aid in nerve identification and early detection of functional impairment. With the evolution of technique, intermittent monitoring has given way to continuous-IONM. Over the years, IONM gathered both support and flak. Despite numerous randomised studies, systematic reviews, and meta-analyses, there still prevails a state of clinical equipoise concerning the utility of IONM and its cost-effectiveness. This article inspects the true usefulness of IONM, elaborates on the optimal way to practice it, and presents a critical literature review.

Existing guidelines recommend lobectomy/hemithyroidectomy (HT) for low-risk thyroid cancer. They are considered safer with lesser complications compared to total thyroidectomy. However, HT is also associated with certain complications. We conducted this retrospective clinical audit of all patients who underwent HT for DTC in our institute from January 2012 to December 2018. The aim of the study was to assess the complications following HT and the follow-up of these patients subsequently. A total of 128 patients satisfied the eligibility criteria. The majority of the patients were women (n = 103, 80.5%). The median age of the patients was 36.5 years (range: 19–77 years). Neck swelling was the most common presentation. All patients underwent conventional open hemithyroidectomy. Five patients had 1–2 metastatic nodes in the central compartment; however, none had metastatic nodes in the lateral neck. Biochemical hypocalcemia (n = 16, 12.5%) was the most common postoperative complication followed by recurrent laryngeal nerve palsy (n = 5, 3.9%). Twenty-six patients developed hypothyroidism at a median duration of 6.5 months following HT necessitating replacement therapy. None of the patients developed recurrence during follow-up (median of 27.5 months). HT is a feasible treatment option for patients with carefully selected cases of DTC. However, HT is also associated with certain complications that should be kept in mind, and patients should be counseled accordingly.

Laryngeal and hypopharyngeal carcinoma are among the common head and neck cancers causing considerable swallowing dysfunction. The functional status of the organ (larynx) is an important point of contention while considering the patients for organ preservation protocol. The aim of this retrospective study was to assess the swallowing status in stage III/IV laryngeal and hypopharyngeal carcinoma and its influence on treatment decision. We evaluated all treatment naive patients who were referred to the swallowing clinic in 2017 (Jan–Dec) for assessment of swallowing prior to treatment initiation. One hundred patients satisfied the eligibility criteria and were included in the study. The site and stage of laryngeal and hypopharyngeal cancer cases were almost equal in number. Their median age was 58 years. Fiberoptic endoscopic evaluation of swallowing (FEES) was done in all patients. 30% of the patients only had swallowing difficulties. Only advanced T-stage (p = 0.04) had an influence on the pretreatment swallowing status. Thirty-seven patients required nasogastric tube (NGT) for feeding. By 2 month post-treatment completion, most patients on NGT could resume oral feeding. Pretreatment swallowing assessment alone did not significantly seem to influence our decisions for organ preservation treatment. However, patients with aspiration could be identified and managed appropriately. Most patients on NGT could resume oral feeds post-treatment completion.

Background: Overburdened systems and concerns of adverse outcomes have resulted in deferred cancer surgeries with devastating consequences. In this COVID pandemic, the decision to continue elective cancer surgeries, and their subsequent outcomes, are sparsely reported from hotspots. Methods: A prospective database of the Department of Surgical Oncology was analysed from March 23rd to April 30th, 2020. Findings: Four hundred ninety-four elective surgeries were performed (377 untested and 117 tested for Covid 19 before surgery). Median age was 48 years with 13% (n = 64) above the age of 60 years. Sixty-eight percent patients were American Society of Anaesthesiology (ASA) grade I. As per surgical complexity grading, 71 (14·4%) cases were lower grade (I-III) and 423 (85.6%) were higher grade complex surgeries (IV – VI). Clavien-Dindo ≥ grade III complications were 5.6% (n = 28) and there were no postoperative deaths. Patients >60 years documented 9.3% major complications compared to 5.2% in

Swallowing after total laryngectomy (TL) is altered and the swallowing related issues are largely underreported. It is important to identify factors that may negatively influence swallowing after TL in order to rehabilitate these patients appropriately. The study included patients who underwent TL from June 2015 to November 2017 for laryngeal and hypopharyngeal malignancy. Sequential swallowing assessment was done in these patients over time. The assessments were done using the FOIS scale and the PSS-HN normalcy of diet scores and analysed to assess the presence of swallowing related issues, factors influencing swallowing and its recovery over time. Sixty-seven who underwent total laryngectomy (TL) were included in the study. Swallowing assessments were done once in 3 months. Overall there was an improvement in swallowing over time. Both the FOIS (Median score of 3.82 in first to 5.77 in the fifth visit) and the PSS-HN scores (median score of 33.63 at first visit to 63.66 at fifth visit) improved over time. Patients undergoing TL after treatment failure with chemoradiotherapy (p value

Summary Hypoxia within the tumor microenvironment (TME) is a key factor contributing to immunosuppression in tumors, co-relating with poor treatment outcome and decreased overall survival in advanced oral cancer (OC) patients. Vδ2 is a dominant subset of gamma delta T cells (γδT cells) present in the peripheral blood which exhibits potent anti-tumor cytotoxicity and is evolving as a key player of anti-cancer cellular therapy. However, the fate of γδT cells in hypoxic oral tumors remains elusive. In the present study, we compared the effect of hypoxia (1% O2) and normoxia (21% O2) on the expansion, proliferation, activation status, cytokine secretion and cytotoxicity of γδT cells isolated from OC patients and healthy individuals. Hypoxia-exposed γδT cells exhibited reduced cytotoxicity against oral tumor cells. Our data demonstrated that hypoxia reduces the calcium efflux and the expression of degranulation marker CD107a in γδT cells, which explains the decreased anti-tumor cytotoxicity of γδT cells observed under hypoxia. Hypoxia-exposed γδT cells differentiated to γδT17 [γδ T cells that produce interleukin (IL)-17] cells, which corroborated our observations of increased γδT17 cells observed in the oral tumors. Co-culture of γδT cells with CD8 T cells in the presence of hypoxia showed that programmed cell death ligand 1 (PD-L1)high γδT cells brought about apoptosis of programmed cell death 1 (PD-1)high CD8 T cells which could be significantly reversed upon blocking PD-1. Thus, future immunotherapeutic treatment modality for oral cancer may use a combined approach of blocking the PD-1/PD-L1 signaling and targeting hypoxia-inducible factor 1α, which may help in reversing hypoxia-induced immunosuppression.

The ATA guidelines for differentiated thyroid cancer (DTC) are one of the most widely referred to. Their 2015 edition proposed a new risk stratification system and modified the indications for radioactive iodine (RAI) ablation especially for the low risk category. We attempted to analyze whether the new guidelines altered referral practices for RAI ablation at our institute. Patients who underwent total or completion thyroidectomy for DTC during 2016–2017 were included. Relevant demographical and pathological data was tabulated. Patients were classified as per the new stratification system and referral practice for RAI ablation documented. 238 patients were included. Of these 20.6% were low risk, 44.1% were intermediate and 35.3% were high risk as per modified guidelines. All patients within the intermediate and high-risk group and 77.8% of the low risk group were referred for RAI ablation. Analysis of risk factors revealed that within the low risk group there were three patients with

// Vanita Noronha 1 , * , Vijay Maruti Patil 1 , * , Amit Joshi 1 , Manoj Mahimkar 2 , Usha Patel 2 , Manish Kumar Pandey 2 , Arun Chandrasekharan 1 , Hollis Dsouza 1 , Atanu Bhattacharjee 3 , Abhishek Mahajan 1 , Nilesh Sabale 1 , Jai Prakash Agarwal 4 , Sarbani Ghosh-Laskar 4 , Ashwini Budrukkar 4 , Anil K. D’Cruz 5 , Pankaj Chaturvedi 5 , Prathamesh S. Pai 5 , Devendra Chaukar 5 , Sudhir Nair 5 , Shivakumar Thiagarajan 5 , Shripad Banavali 1 and Kumar Prabhash 1 1 Department of Medical Oncology, Tata Memorial Hospital, HBNI, Mumbai, India 2 Mahimkar Laboratory, Cancer Research Institute (CRI), Advanced Centre for Treatment Research and Education in Cancer (ACTREC), Tata Memorial Centre (TMC), HBNI, Navi Mumbai, India 3 Section of Biostatistics, Department of Epidemiology, Advanced Centre for Treatment, Research and Education in Cancer, Navi Mumbai, India 4 Department of Radiation Oncology, Tata Memorial Hospital, HBNI, Mumbai, India 5 Department of Head and Neck Surgery, Tata Memorial Hospital, HBNI, Mumbai, India * These authors contributed equally to this work Correspondence to: Kumar Prabhash, email: kumarprabhashtmh@gmail.com Keywords: HPV negative; oropharynx; nimotuzumab; weekly; cisplatin Received: September 03, 2019 Accepted: December 21, 2019 Published: January 28, 2020 ABSTRACT Background: Addition of nimotuzumab to weekly cisplatin and radiation improves outcomes in head and neck cancer. HPV negative oropharyngeal cancer has unsatisfactory treatment outcomes and is a candidate for escalation of treatment. We wanted to determine whether the addition of nimotuzumab to cisplatin-radiation could improve outcomes in these poor-risk tumors. Methods: This was a subgroup analysis of a phase 3 randomized study. In this study, locally advanced head and neck cancer patients undergoing definitive chemoradiation were randomly allocated to weekly cisplatin (30 mg/m2 IV)- radiation (66–70 Gy) {CRT arm} or nimotuzumab (200 mg weekly) -weekly cisplatin (30 mg/m2)-radiation (66–70 Gy) {NCRT arm}. The data of HPV negative oropharyngeal cancer was extracted from the database of this study for the analysis. HPV testing was done with p16 immunohistochemistry (IHC) staining and reported according to the CAP criteria. The outcomes assessed were progression-free survival (PFS), disease-free survival (DFS), locoregional control, and overall survival (OS). Interaction test was performed between the study arms and HPV status prior to doing any HPV specific analysis for each of the studied outcomes. Kaplan Meier estimates for 2 year OS with 95%CI was calculated. The hazard ratio was obtained using COX regression analysis. Results: We had 187 HPV negative oropharyngeal cancers, 91 in the CRT arm and 96 in NCRT arm. The interaction test was significant for PFS ( p = 0.000), locoregional control ( p = 0.007) and overall survival ( p = 0.002) but not for DFS ( p = 0.072). The 2- year PFS was 31.5% (95%CI 21.5–42) in CRT arm versus 57.2% (95%CI 45.8–67.1) in NCRT arm (HR -0.54; 95%CI 0.36–0.79, p = 0.002). The 2-year LRC was 41.4% (95%CI 29.8–52.6) in the CRT arm versus in 60.4% (95%CI 48.7–70.2) in the NCRT arm (HR -0.61; 95%CI 0.4–0.94, p = 0.024). The addition of nimotuzumab also lead to an improvement in 2-year OS from 39.0% (95%CI 28.4–49.6) to 57.6% (95%CI 46.3–67.4) (HR-0.63, 95%CI 0.43–0.92, p = 0.018). Conclusions: The addition of nimotuzumab to weekly cisplatin-radiation improves outcomes inclusive of OS in HPV negative oropharyngeal cancers.

Background: Sinonasal tumors are a rare group of neoplasms with limited data available regarding their treatment. Objectives: To estimate the 5 year outcomes and late adverse events of locally advanced sinonasal tumors treated with neoadjuvant therapy (NACT) followed by local therapy. Methods: Twenty-five patients with locally advanced esthesioneuroblastoma or sinonasal neuroendocrine tumors treated between August 2010 and August 2014 with NACT followed by local therapy were selected. The 5-year outcome and late adverse events (CTCAE version 4.02) were noted. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. COX regression analysis was used to identify factors impacting PFS and OS. Results: The median follow-up was 5.15 years. The 5-year PFS in the esthesioneuroblastoma cohort and in the sinonasal neuroendocrine carcinoma (SNEC) cohort was 63.5% (95% confidence interval [CI]: 28.9–84.7) and 34.6% (95% CI: 10.1–61.1), respectively (P = 0.1). The only factor impacting PFS on multivariate analysis was a response to NACT (P = 0.033). The 5-year OS in the esthesioneuroblastoma cohort and in the SNEC cohort was 91.7% (95% CI: 53.9–98.9) and 46.2% (95% CI: 19.2–69.6), respectively (P = 0.024). Any grade late adverse events were seen in 20 patients (80%). Metabolic late adverse events were seen in 19 patients (76%). Conclusion: NACT in advanced sinonasal cancers is associated with an improvement in 5-year outcomes. However, late side effects, especially metabolic, are seen in these patients and should be evaluated during follow-up.

Varying evidence exists surrounding skip metastasis in clinically node-negative oral cancer. We aim to report its incidence, identify factors predicting its presence, and determine survival outcomes to possibly decide "adequacy" of neck dissection for this select group.A review of audit records (clinical and pathologic) was undertaken to identify early stage (cT1/T2 cN0) oral squamous carcinoma patients operated between January 2016 and December 2020. Skip metastasis was defined as presence of nodal metastases distant from the primary tumour and at a lower level without metastases at levels above this. The factors predicting its presence were determined using chi-square and multivariate tests. Survival analysis was performed using Kaplan-Meier and regression hazard models.Occult metastasis rate was 17.9 % among 761 patients, with 47.1 % travelling to level I. Skip metastasis at level III was seen in 1.2 % and level IV was 0.3 %. Presence of PNI predicted the presence of skip metastasis at level III (p = 0.041, OR-0.241, 95 %CI 0.062-0.942) and no significant factors were identified for level IV. The 5-year disease-free survival was significantly reduced with isolated level IV metastasis (50 % vs 79.6 %, p = 0.017). Isolated occult metastasis at level Ia was in 0.3 %, all from tongue cancers. Their presence did not impact the 5-year overall survival (100 % vs 90.7 %, p = 0.628) and disease-specific survival (100 % vs 92.5 %, p = 0.675).The negligible incidence of skip metastasis to level IV in a clinically node negative neck suggests that clearance up to level III might be adequate in a large majority of patients.

The swallowing outcomes in patients undergoing glossectomy have been inconsistently reported in the literature owing to variable follow up times, different tools for assessment and lack of single institution large scale studies. The aim of our study was to assess the patterns of swallowing outcomes over time and identify factors affecting nasogastric tube dependency at 1-year post-surgery.This was a retrospective study of treatment naïve patients with oral tongue carcinoma who underwent surgery and attended the speech and swallow clinic between January 2016 and December 2019 at our institute were included in the study. The findings of swallowing assessment by a speech language pathologist at three time points were recorded.A total of 606 patients were found eligible for the study. The median age of the patients was 50 years with the 211 (34.8%) patients having T3/T4 disease. The swallowing outcomes in terms of tube dependence and the spectrum of diet tolerance seem to improve over time with an increasing number of patients switching over to a solid diet by 1 year. A higher defect class (HR = 24.43 [3.48-171.27]) and presence of co-morbidities (HR = 4.17 [1.59-10.92]) were associated with sustained feeding tube dependency status at 1 year. A nomogram was developed based on these findings.The swallowing outcomes in terms of tube dependence and the spectrum of diet tolerance seem to improve over time. A higher defect class and presence of co-morbidities were associated with NGT dependency at 1 year.

Adjuvant re-chemoradiation after salvage surgery improves disease-free survival in recurrent head and neck cancer. However, most patients are ineligible for re-irradiation and are kept on observation. We investigated the efficacy of metronomic adjuvant chemotherapy (MAC) in this group of patients compared to observation.This was a randomized integrated phase II/III clinical trial. Adults with recurrent head and neck cancer, who had undergone salvage surgery, but were ineligible for adjuvant re-irradiation were randomized in a 1:1 ratio to either MAC arm or observation. MAC consisted of weekly oral methotrexate (at a dose of 15 mg per square meter of body surface area) and celecoxib (at a dose of 200 mg orally twice daily) for 6 months. The primary endpoint of phase 2 was disease-free survival (DFS) while that of phase 3 was overall survival (OS). For phase 2, to detect an improvement in the hazard ratio (HR) 0.67 with MAC, with a type 1 error of 10% (1-sided), type 2 error of 30%, 105 patients were required. While for phase 3, with a target HR of 0.77, with a type 1 error of 5%, type 2 error of 20%, 318 patients were required. Here we report the results of phase 2 part of the study.At a median follow up of 30.2 months (95% confidence interval (CI), 25.3 to 35.1) the 1 year and 2-year DFS were 57.4% (95% CI, 42.8-69.5) and 37.6% (95% CI, 24.1-51) in MAC arm whereas the corresponding numbers were 62.3% (95% CI, 47.8 to 73.8) and 54.2%(95% CI, 39.8 to 66.5) in observation arm, respectively (hazard ratio for progression, 1.45; 95% CI, 0.87 to 2.47; P = 0.15). In the MAC arm, the 1 and 2 year OS was 78.7% (95% CI, 64.9 to 87.6) and 48% (95% CI, 34.1 to 62).The corresponding figures in the observation arm were 79.2% (95% CI, 65.7 to 87.9) and 65.5% (95% CI, 50.9 to 76.7) (hazard ratio for death, 1.7, 95% CI, 0.94 to 3.08; P = 0.08).The adjuvant 6-month metronomic schedule was ineffective in improving outcomes in recurrent head and neck cancers post salvage surgery who are ineligible for re-radiation.Clinical trial registry of India (CTRI)- CTRI/2016/04/006872 [Registered on 26/4/2016].

BackgroundThere is controversy regarding management of the neck at salvage laryngectomy. The aim of this study was to perform an analysis to determine the incidence of occult node positivity in this group and analyse factors affecting it.MethodA retrospective analysis of 171 patients who underwent salvage total laryngectomy between 2000 and 2015 for recurrent or residual disease following definitive non-surgical treatment and were clinico-radiologically node negative at the time salvage laryngectomy was carried out.ResultsA total of 171 patients with laryngeal or hypopharyngeal cancers underwent concurrent neck dissection at laryngectomy. There were 162 patients (94.7 per cent) who underwent bilateral neck dissection, and 9 patients (5.3 per cent) who underwent ipsilateral neck dissection. The occult lateral nodal metastasis rate was 10.5 per cent. Of various factors, initial node positive disease was the only factor predicting occult metastasis on univariable and multivariable analysis (p = 0.001).ConclusionRisk of occult metastasis is high in patients who have node positive disease before starting radiotherapy. This group should be offered elective neck dissection.

India accounts for almost a third of the global burden of oral cancer, a situation worsened by the inability to afford care. When available, aid is often insufficient, and costing is based on informal estimations. This study objectively determines direct healthcare costs of oral cancer in India. The study was performed from a healthcare provider’s perspective using a validated bottom-up method. Care pathways were determined by prospectively observing the natural management of 100 oral cancer patients treated between October 2019 and March 2020. Specific costing categories were built across services, and apportioned values for each interaction was averaged. Costs of treatment and service utilisation were obtained using probabilistic sensitivity analyses. The unit cost of treating advanced stages (United States Dollar (USD) 2,717) was found to be 42% greater than early stages (USD1,568). There was an 11% reduction in unit costs with increases in socioeconomic status. Medical equipment accounted for 97.8% of capital costs, with the highest contributor being imaging services. Variable costs for surgery in advanced stages were 1.4 times higher than early stages. Compared to surgery alone, the average cost of treatment increased by 44.6% with adjuvant therapy. These results show that over the next decade, India will incur an economic burden of USD 3 billion towards the direct healthcare of oral cancer. Early detection and prevention strategies leading to 20% reduction in advanced stage disease could save USD 30 million annually. These results are critical to deliver a disease-driven and objective reform for oral cancer care.

BACKGROUND The primary aim of this study was to evaluate the therapeutic efficacy and outcome of 177 Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) in somatostatin receptor-positive metastatic medullary thyroid carcinoma (MTC), including progression-free survival (PFS) and overall survival (OS), and also to determine the various prognostic variables. The secondary aim was toxicity assessment of PRRT in this group of patients. METHODS A total of 43 somatostatin receptor-positive metastatic MTC patients, treated with 177 Lu-DOTATATE PRRT in a large tertiary care center, were included in this analysis. After receiving the therapy, post-treatment response evaluation was undertaken for symptomatic and biochemical responses (serum calcitonin) and imaging responses with 68 Ga-DOTATATE, 18 F-FDG PET-CT, CeCT (PERCIST and RECIST 1.1 criteria). Calcitonin doubling time (CtnDT) was calculated by the American Thyroid Association calculator. The adverse events were graded according to the NCI-CTCAE v5.0 criteria. The observed Kaplan-Meier curves for both PFS and OS since first PRRT were compared with CtnDT (more than 24 months vs less than 24 months) by log-rank (Mantel-Cox) test. The prognostic variables were investigated for their association with CtnDT and response to PRRT using Cox proportional-hazards model. RESULTS The median OS was 26 months (95% CI 16.6-35.3 months) and the median PFS 24 months (95%.CI: 15.1-32.9 months). Following 177Lu-DOTATATE PRRT, the observed median PFS and OS was longer in patients who had CtnDT more than 24 months compared to those with CtnDT less than 24 months (median PFS not yet reached vs 10 months and median OS 60 months vs 20 months). Assessing from the time-point of first 177 Lu-DOTATATE PRRT cycle, the patients with CtnDT more than 24 months had a significantly longer PFS (P

The description for T4a oral tongue cancer in the 8th edition AJCC staging can be improved further. In this article we attempted to identify the important radiological (MRI) findings that could possibly be included in the staging eventually.We included all oral tongue squamous cell carcinoma patients who underwent surgery at TMH between Jan 2012 to Dec 2018 and whose MRIs were available for review. The relation of the tumor to the neurovascular bundle (NVB) on MRI was classified as Type I to IV. The association of the type of NVB involvement with DFS and the presence of PNI in the final HPR was analyzed.Two-hundred and fifty-nine patients satisfied the eligibility criteria. The majority of them were men (82.6%), with a median age of 49 Yrs. Sixty-nine percent of patients had either abutment (Type III) or encasement (Type IV) of the NVB. The presence of Abutment/encasement of the NVB was significantly associated with the presence of PNI in the final HPR (p 0.001). This abutment/encasement was seen in clinically advanced T-stage tumors. However, the presence of abutment/encasement of the NVB influenced the DFS in the univariate analysis only.Abutment/encasement of the NVB in patients with carcinoma oral tongue is often seen in advanced-stage tumors and is significantly associated with the presence of PNI in the final HPR. Hence, the relation of the tumor with the NVB should be further assessed to understand its importance and its possible inclusion in the AJCC T-staging.

Background To assess the efficacy of intensity-modulated radiation therapy (IMRT) for tumors of the nasal cavity and paranasal sinus (PNS) region. Materials and methods Two hundred fourteen patients with tumors of the nasal cavity and PNS region treated with curative intent IMRT between 2007 and 2019 were included in this retrospective analysis. Results Fifty-one (24.1%) received definitive RT/CTRT and 163 (75.9%) received adjuvant RT. Most common histology was squamous cell carcinoma (26.1%) followed by adenoid cystic carcinoma (21.5%). The median follow-up was 43.5 months. The 5-year local control (LC), event-free survival (EFS), and overall survival (OS) for the entire cohort was 66.9%, 59%, and 73.9%, respectively. On univariate analysis treatment with nonsurgical modality, T classification and undifferentiated/poorly differentiated histology were associated with inferior 5-year LC, EFS, and OS. Four patients had late Grade 3/Grade 4 ocular toxicity. Conclusions IMRT should be the standard of care for tumors of PNS region across all histologies and treatment setting.

6058 Background: Depth of invasion (DOI) has been incorporated in the new AJCC TNM staging (8th edition) for oral cancers. We hypothesized that the negative effect of increasing DOI on outcomes was a result of an increased propensity to node metastasis and appropriate neck treatment would negate its detrimental effect on outcomes. Methods: Patients with T1/ T2 oral squamous cell carcinoma, clinically node negative, from a previously reported Randomized Controlled Trial (NCT 00193765) formed the cohort for this study. Patients were restaged according to the new staging system . Overall survival(OS) was estimated by the revised T stage for the entire cohort and separately for those who underwent END and those who did not (TND arm) using Kaplan Meier and log rank test . Multivariate analysis was performed using Cox proportional hazard model making adjustment for neck treatment, T stage, site, prognostic factors and the interaction between revised T stage and neck treatment. Results: Of the 596 patients 577 were evaluable, with a median follow up of 77.57 months. Initial pT staging was pT1, 389(67.4%); pT2, 181(31.4%); pT3, 7(1.2%) and was modified to pT1, 195(33.8%); pT2, 280(48.5%); pT3, 102(17.7%) on restaging . 288 patients underwent END and 289 did not (TND arm). For the entire cohort 5-year OS rates were 79.0% [95 %CI, 73.12-84.88] for pT1, 69.4% [95% CI, 63.91-74.89] for pT2 and 53.0% [95% CI, 43.2 -62.8] for pT3 with significant difference between the 3 groups (p < 0.001). In those without upfront neck treatment( TND ), OS difference was maintained between the pT1 and pT2 groups [81.1% (95%CI, 73.26-88.94) vs 65.0% (95%CI, 56.77-73.23)], p = 0.004. This difference was not apparent in the END arm ,pT1 -76.9% (95 %CI, 68.47-85.33) vs pT2 -73.7% (95%CI, 66.25-81.15), p = 0.73. T3 tumours had uniformly poor survival irrespective of neck treatment. On multivariate analysis of the revised pT1/T2 cohort (n = 475), pT stage, neck treatment and grade were independent prognostic factors impacting OS. There was a significant interaction between the T stage and neck treatment (p = 0.03). Conclusions: When DOI < 10 mm, END supplants the prognostic implication of depth with similar outcomes for T1 and T2 tumours (new AJCC staging). The exact role of DOI on outcomes warrants further research. Clinical trial information: NCT00193765.

Thyroid withdrawal in preparation for radioiodine ablation (RIA) may have a profound impact on health-related quality of life (HRQL). Cost implications and scheduling limit the use of recombinant TSH and triiodothyronine (T3) with its shorter half-life is a conceptually attractive alternative. Prospective cohort study design with patients having withdrawal of thyroxine (n = 37) or T3 supplementation (n = 33). HRQL was assessed using EORTC QLQ-C30, QLQ-H&N35 and modified Billewicz questionnaires. Time interval to achieve optimal TSH levels (at least 30 mIU/ml) prior to RIA was determined. With the exception of emotional domain (QLQ-C30 p = 0.045), LT3 supplementation did not confer significant benefit when compared to LT4 withdrawal. Target serum TSH levels was achieved in 95% of patients by week 4 post thyroidectomy. LT3 supplementation delivered equivocal benefit and therefore the alternate strategies to minimize the impact on HRQL of reduction in the duration of hypothyroidism in T4 withdrawal are suggested.

Context: Eyelid carcinoma is rare tumors of the head and neck. They are rarely lethal but can be associated with significant morbidity if not treated early and appropriately. There are limited data available from world over and in particular the Indian subcontinent regarding eyelid carcinoma and its prognostic factors influencing treatment outcomes. Setting and Design:Retrospective study of patients treated in a tertiary cancer center between 2005 and 2016. Methodology: In this study, 51 patients with eyelid carcinoma treated at single tertiary cancer center were included. The demographic, clinical data, which includes the treatment received, histopathology report and follow–up, were recorded. All the relevant variables influencing disease-free survival (DFS) were analyzed. Results: Sebaceous carcinoma was the most common eyelid carcinoma followed by squamous cell carcinoma and basal cell carcinoma in descending order in this series. Lower eyelid was involved most often. The incidence of nodal metastasis was low (14%). Multivariate analysis revealed that margin status influenced the DFS (P= 0.001) (hazard ratios = 15.9 [95% confidence interval: 1.8–135.2]). The 5 years' DFS was 70%. Conclusion: Eyelid tumors are less common cancer with good prognosis if treated appropriately. The morbidity associated with treatment can be reduced if treated early.

Parathyroid cancer is a rare endocrine malignancy with only a few thousand cases reported worldwide. As a result, there exists considerable controversy regarding the various aspects of this disease, viz., etiology, diagnosis, and management. We hereby attempt to review the literature on parathyroid carcinoma (PC) and summarize the practices based on the current evidence available. The majority of the PC are sporadic although an association with hyperparathyroidism-jaw tumor syndrome, multiple endocrine neoplasia (MEN) 1 and 2, and isolated familial hyperparathyroidism has been shown. As preoperative diagnosis is challenging, PC should be suspected in patients presenting with a neck mass with signs and symptoms of invasion to surrounding structures. Skeletal and renal symptoms are often associated with PC as presenting complaints. The biochemical parameters are more pronounced in the case of PC compared with benign countpart. Due to its rarity, the American Joint Committee of cancer control (AJCC) acknowledges that as yet a clear distinct staging system to prognosticate the disease would be premature. Complete excision with negative margins at first surgery offers the best chance of cure. The role of radiotherapy (RT) is still unclear; however few series have suggested a better locoregional control with adjuvant RT. Recurrences are common and are most significantly associated with an incomplete clearance at initial surgery. Surgical salvage of recurrent/metastatic disease with medical management of hypercalcemia is the treatment of choice. Large prospective studies and trials need to be conducted to understand the pathology better and improve management protocols; however this is a challenge due to rarity of cases.

Among the reconstructive options available for buccal mucosa defects with an intact mandible, free flap with microvascular anastomosis is the best option. However, in the developing world, with poor resources, limited in- frastructure, and high patient load, this cannot be offered to all patients. We report on the success of the masseter flap for reconstruction of such defects in carefully selected patients. Despite some known limitations, this flap is easy to learn and carries acceptable complications. The results of this flap may not be comparable to those of microvas- cular reconstructions, but they are better than those from other options such as skin graft, nasolabial flap, submental flap, etc. in terms of surgical time required, no donor site morbidity, and minimal aesthetic deformity.